The inheritance of variability in the behavioral and physiologic effects of d-amphetamine is being studied. A small dose of amphetamine (0.3 mgm/kg) was administered to normal volunteer twins after medical and psychiatric screening. Identical twins are highly concordant in behavioral responses, growth hormone and prolactin changes, measures of sleeplessness and attention, and baseline 3-methoxy-4-hydroxyphenylglycol (MHPG). Behavioral response to amphetamine is highly predictable from baseline measures of MHPG and prolactin. A cholinergic agonist, arecoline, has been used to test the REM-induction response in identical twins. Preliminary results indicate that this response is not heritable. Cortisol response to arecoline has also been tested in normal volunteers, where a threshold dose for plasma cortisol increase has been identified.